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Chronic Lymphocytic LeukemiaPhase 1NCT03447808

Daratumumab and Ibrutinib in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia

A Phase 1 study testing Daratumumab, Ibrutinib and Laboratory Biomarker Analysis in people with Chronic Lymphocytic Leukemia, run by Jennifer Woyach at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase Ib trials studies the side effects of daratumumab and ibrutinib and how well they work in treating patients with symptomatic chronic lymphocytic leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Daratumumab, Ibrutinib and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
16 Aug 2018to 26 May 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of chronic lymphocytic leukemia (CLL) meeting criteria established in the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for the diagnosis and treatment of CLL
  • Requires therapy for symptomatic CLL in the opinion of the treating physician as defined by:
  • Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
  • Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
  • Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
  • Constitutional symptoms, which include any of the following:
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  • Unintentional weight loss of 10% or more within 6 months
  • Significant fatigue limiting activity
  • Fevers >= 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
  • Night sweats > 1 month without evidence of infection
  • No prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL with the exception of palliative loco-regional radiotherapy and corticosteroids for symptom control
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin >= 8 g/dL
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelets >= 30,000/mm^3
  • Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x ULN
  • Total bilirubin =<1.5 x ULN (excepting Gilbert?s syndrome)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (unless due to liver involvement)
  • Serum creatinine < 2.0 mg/dL OR creatinine clearance (Cockcroft) >= 40 mL/min/1.73 m^2
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for females, these restrictions apply for 1 month after the last dose of study drug; for males, these restrictions apply for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • Positive hepatitis serology:
  • Hepatitis B virus (HBV): Patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B virus core antibody (anti-HBc); patients who are positive for anti-HBc may be considered for inclusion in the study on a case-by-case basis if they are hepatitis B viral deoxyribonucleic acid (DNA) negative and are willing to undergo ongoing HBV DNA testing by real-time polymerase chain reaction (PCR); patients with positive serology may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management
  • Patients with positive hepatitis B surface antigen (HBSAg) consistent with prior vaccination to HBV (i.e., hepatitis B virus surface antibody [anti-HBs]+, anti-HBc-) may participate
  • Patients suspected to have false positive serologic studies because of IV immunoglobulin administration are potentially eligible after negative PCR studies for viral DNA/ribonucleic acid (RNA) and discussion with the principal investigator
  • Hepatitis C virus (HCV): Patients with positive hepatitis C serology unless HCV RNA is confirmed negative and may be considered for inclusion in the study on a case-by-case basis (e.g., patients with negative viral load after HCV-specific treatment)

Who cannot join

  • Patients who have had chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 28 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier; steroids for control of disease related symptoms are permitted
  • Patients who are receiving any other investigational agents
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Active Richter's transformation
  • Known active involvement of the central nervous system by lymphoma or leukemia
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  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon); patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant
  • Requires chronic treatment with strong CYP3A inhibitors
  • Known infection with the human immunodeficiency virus (HIV) virus
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association functional classification
  • History of severe (defined as grade 4 and/or requiring permanent discontinuation of prior antibody therapy) allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
  • A female patient who is pregnant or breast-feeding
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] < 50% of predicted normal), persistent asthma, or a history of poorly controlled asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
  • History of other active malignancies other than CLL within the past 3 years prior to study entry, with the exception of adequately treated in situ carcinoma or the cervix uteri or breast, basal cell or localized squamous cell carcinoma of the skin, previous malignancy confirmed and surgically resected (or treated with other modalities) with curative intent or without relapse for >= 2 years
  • Vaccination with a live vaccine < 28 days prior to the start of treatment
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator?s opinion, could compromise the subject?s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Daratumumab and Ibrutinib for Symptomatic, Treatment-Naive CLL: A Phase 1b Proof-of-Concept Study

This phase Ib trials studies the side effects of daratumumab and ibrutinib and how well they work in treating patients with symptomatic chronic lymphocytic leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daratumumab and ibrutinib may work better in treating patients with chronic lymphocytic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To characterize the safety of treatment with daratumumab and ibrutinib for previously untreated chronic lymphocytic leukemia (CLL).

II. To determine the complete response rate (CR) at the post cycle 12 response assessment following treatment with daratumumab and ibrutinib for previously untreated chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

  1. To characterize the activity of daratumumab and ibrutinib as measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and time-to-next treatment.

TERTIARY OBJECTIVES:

  1. To measure pharmacodynamic parameters in B cells including drug occupancy of BTK and B cell receptor signaling during treatment.

II. To determine the influence of this combination on T cell and natural killer (NK) cell number and function.

III. To assess for development of mutations that may confer resistance to this combination.

IV. To assess the ability of daratumumab to clear CLL in the peripheral blood and association of CD38 expression on CLL cells with response.

OUTLINE:

Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Beginning course 2, patients also receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.

Being tested
Daratumumab, Ibrutinib, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabBiological

    Also called Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

    Given IV

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT03447808
Study groupRoleWhat they receive
Treatment (daratumumab, ibrutinib)ExperimentalPatients receive daratumumab IV on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Beginning course 2, patients also receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Daratumumab; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete response (CR) + complete response with incomplete marrow recovery (CRi) defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria

    Measured: Up to 2 years

  2. Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Will be tabulated by type and grade and displayed in summary form.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Duration of response (DOR)

    Will be summarized by the Kaplan-Meier method.

    Measured: From the date of first response until the date of progression or death presumed attributable to disease progression, whichever occurs first, assessed up to 2 years

  2. Overall survival

    Will be summarized by the Kaplan-Meier method.

    Measured: From the first treatment date until the date of death or date last known alive, assessed up to 2 years

  3. Overall survival (CR + CRi + partial response [PR])

    With a 95% confidence interval (CI) will be reported for all evaluable patients, assuming a binomial distribution.

    Measured: Up to 2 years

  4. Progression-free survival

    Will be summarized by the Kaplan-Meier method.

    Measured: From the first treatment date until the date of progression or death, whichever occurs first, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2018
  2. Study start16 Aug 2018
  3. Primary completion26 May 2026
  4. Study completion26 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03447808
Sponsor's protocol ID
OSU-17143
Other IDs
NCI-2018-00159
Status last verified
May 2025
First submitted
21 Feb 2018
Last updated
15 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daratumumab, Ibrutinib and Laboratory Biomarker Analysis in people with Chronic Lymphocytic Leukemia, run by Jennifer Woyach at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response (CR) + complete response with incomplete marrow recovery (CRi) defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03447808.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.

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